Autonomic Nervous System Flashcards
ANS functions
. Innervates smooth muscle, heart and glands
. AP in nerve can result in excitation or inhibition of effector cells
. Autonomic reflexes control organ function
. 2 neurons btw CNS and effector organ
. Slower conduction: longer, less focused response
SNS functions
. Innervates skeletal muscle . AP in nerve always results in contraction of skeletal muscle . Under voluntary control . 1 neuron btw CNS and muscle . Faster conduction, focused response
ANS divisions
. sympathetic
. Parasympathetic
. Enteric
. Maintain homeostasis
Single innervation target organs
. Sweat glands . Peripheral blood vessels . Hair follicles . Brown adipose . Adrenal medulla . Kidney
Dual innervation target organs
. Eye . Salivary glands . Lung . Heart . Enteric nervous system . Pancreas . Liver . Bladder . Reproductive organs . Blood vessels of external genitalia
SNS
. Thoracolumbar
. Preganglionic axons leave in ventral root, enter paravertebral ganglion through white rami
. Go through paravertebral or prevertebral ganglia (1 plexus in front of aorta)
. Preganglionic fibers synpase w/ postganglionic neurons or travel for several segments before forming synapses w/ postganglionic neurons
. Postganglionic axons leave ganglia through gray communicating rami to enter spinal n.
. Prevertebral plexus forms by celiac, sup., and inf. Mesenteric ganglia
PNS
. Craniosacral
. Preganglionic cell bodies in nuclei of brain stem and S2-4
. Preganglionic fibers from upper nuclei distribute w/ 4 cranial nn (III, VII, IX, and X) and from sacral segments go w/ sacral nn.
Autonomic reflexes
. Afferent neurons activated by stimulus
. Afferent signal integrated in CNA
. Efferent autonomic neurons activated to modulate target organ function in response to initial stimulus
. Afferent and efferent neurons may innervates the same or different organs
. Efferent arm has preganglionic (in peripheral ganglia) and postganglionic neuron (to target organs w/ varicosities along it’s length to release neurotransmitter)
PNS functions
. Contract pupil . Inc. secretions . Enhance GI motility . Stimulate insulin release . Slow HR . Constrict airway . Vasodilate vessels
SNS functions
. Dilate pupil . Dec. GI motility . Stimulate gluconeogenesis, inhibit insulin . Inc. HR . Inc. arterial pressure . Dilate bronchial smooth muscle . Inc. blood flow to muscle, dec. blood to abdominal organs . Whole body sweating
ACh neurotransmitters
. Cholinergic nn.
. All sympathetic and parasympathetic preganglionic nn.
. Only sympathetic sweat gland postganglionic
. All parasympathetic postganglionic
NE neurotransmitter
. Adrenergic
. All sympathetic postganglionic except sweat glands
. Adrenal medulla releases some into bloodstream
epinephrine
. Released from adrenal medulla after activation of SNS
. Catecholamine
ACh synthesis
. Choline + acetate -> acetyl CoA + CoA -> ACh
NE synthesis
. Tyr -> DOPA -> dopamine -> NE -> E
Characteristics of receptor-neurotransmitter interaction
. Threshold: conc. Of NT where response 1st occurs
. Saturation
. Specificity
. Sensitivity: conc. NT to elicit 50% max response
. Potency: ligand conc. To achieve max response
. Competition
. Agonist
. Antagonist
Magnitude of biological response to a ligand depends on ____
Number of ligand-receptor complexes
. Formation is non-covalent and follows 1st order molecular kinetics
Affinity constant K
. Represents how readily ligand assoc. w/ receptor
. K = [LR]/[L][R]
. K = concentration of ligand when 50% receptor sites are bound
. Lower the K, higher the affinity to receptor
Alpha-1 adrenergic receptors
. Coupled to Gq protein, phospholipase C-IP3-mediated Ca signaling
. Cardiovascular: vascular smooth muscle contraction
. GI: dec. rate and strength of smooth muscle contractions (mediated by cAMP PKA dependent activation of K channels)
. Eye: dilation of pupil (mydriasis
Alpha-2 adrenergic receptors
. Coupled to Gi protein, alpha subunit, dec. adenylate cyclase, cAMP, PKA
. Gi protein beta-gamma subunits inc. K channels
. Endocrine: stimulate gluconeogenesis, dec. insulin, inc. glucagon release
. GI: dec. rate and strength of smooth m. Contraction (mediated by Gi protein-induced reduction of cAMP
. CNS: located in presynaptic terminals as autoreceptors mediated neg. feedback of NE release (presynaptic inhibition)
Beta adrenergic receptors
. Coupled to Gs protein
. Inc. adenylate cyclase
. Inc. cAMP
. Inc. PKA
Beta-1 adrenergic receptors effect on systems
. Cardiovascular: inc. CO, HR, and contractile force of heart
. GI: inc. secretion thick viscous saliva
Beta-2 adrenergic receptor effect on system
. Respiratory: dilation of bronchial smooth m. To open airways
. GI: dec. motility of visceral smooth muscle
. Endocrine: inc. glycogenolysis in adipose tissue
Cholinergic receptors
. ACh receptors
. Muscarinic
. Nicotinic
Muscarinic receptors
. Located on target organs
. M1-M5
. Activation produces excitatory or inhibitory response depending on target organ
. Activation of odd-numbered receptors leads to inc. intracellular Ca through IP3-DAG system
. Activation of even numbered receptors dec. cAMP and PKA
Muscarinic receptors effect on systems
. Eye: contraction of pupil (miosis)
. Cardiovascular: SA node (dec. HR by M2-mediated activation of K channels), vasodilation of vessels
. Respiratory: constriction bronchial smooth muscle
. GI: inc. secretion thin saliva, inc. motility, inc. secretion of digestive enzymes
. Endocrine: inc. insulin secretion, inc. glycogen storage
. Sweat: inc. sweat
. Renal: contract bladder wall during urination
Nicotinic receptors
. Always produces excitatory response in skeletal m. Or autonomic neuron
. Nicotinic-muscle (Nm/N1)
. Nicotinic-neural (Nn/N2)
N1 receptors
. at motor end plate on skeletal muscle
. Voluntary contraction of skeletal m.
N2 receptors
. Located on cell bodies of all postganglionic neurons (sympathetic and parasympathetic)
. Located in adrenal medulla
. Activation of postganglionic sympathetic and parasympathetic neurons
. Antagonists block synaptic transmission in sympathetic and parasympathetic nervous systems
Signal transduction
. Neurotransmitters are hydrophilic and need receptor to cross lipid membrane
. Binding to receptor triggers series of events in cell that cause biological response
Signal amplification
. Single activated enzyme can turn substrate molecules into product
. At each step, another application takes place
. Explains how neurotransmitters can be effective at extremely low concentration
Types of signal transduction
. Receptors that are also ion channels
. Receptors that are protein kinases
. Receptors that interact w/ JAK kinases
. Receptors that are G protein coupled
Receptors that are also on ion channels
. When NT binds to receptor, ion channel opens
. Permits diffusion of ion down their concentration gradient
. Ions entering cell can alter membrane potential and/or act as second messenger itself
. Generate biological response
Receptors that are protein kinases
. Most commonly tyrosine kinase
. Protein phosphorylated by tyrosine kinase generates biological response
Receptors that interact w/ JAK kinases
. Binding of ligand to receptor activates JAK
. JAK phosphorylated specific proteins
. Generates biological response
Receptors that are coupled to G proteins
. Binding of NT to receptor activates G protein by substituting GTP for GDP
. Activated G protein binds to and opens ion channels or activates (or inhibits) a membrane bound enzyme
. Enzyme inc. or dec. generation of 2nd messenger inside cell
.2nd messenger activates a protein kinase that phosphorylates specific proteins that generate biological response
Main second messengers
.cAMP .cGMP . IP3 . DAG . Ca (Ca-calmodulin)
Cyclic AMP pathway
. G-binding regulatory protein (Gs) activates adenylyl cyclase (Gi inhibits adenylyl cyclase)
. Adenylyl cyclase converts Mg-ATP to cAMP
. Hydrolysis of GTP to GDP terminates activation
.cAMP binds to regulatory subunit on cAMP-dependent protein kinase to activate it
. Kinase phosphorylates many proteins to amplify biological response
.cAMP metabolized by phosphodiesterase (PDE) that concerts it to inactive metabolite (5’AMP subunit of protein kinase)
Cyclic GMP pathway
. Generated by guanylyl cyclase
. Main target is cGMP-dependent protein kinase (PKG)
.cGMP directly activates several ion channels or ion pumps that participate in modulating cytoplasmic Ca levels in smooth muscle and sensory tissue
. Activation of ion channels directly by cGMP binding to from phosphorylation by PKG that alters cytoplasmic Ca
. Production regulated by activation of cytoplasmic or membrane localized form of GC
GCs
. Targets of NO produced by endothelial cells
. Pathway mediates smooth muscle relaxation and neurotransmission
IP3 and DAG pathway
. Gq activates membrane bound phospholipase C
. Catalyze breakdown of membrane PIP2 to DAG and IP3
. DAG activates PKC that phosphorylates proteins
. IP3 binds to IP3 receptor (ligand-gated ion channel) in ER to induce Ca release
. Result is inc. intracellular Ca
How Ca induces cellular responses
. Binding to calmodulin
. Combining to other Ca-binding proteins
. Directly binding to and affecting target proteins
Ways to inc. intracellular Ca
. Directly through Ca channels in surface membrane
. Release from intracellular Ca stores
Main intracellular Ca store is ___
. In the ER
Ca release from ER
. Through ryanodine and IP3 ligand-gated receptors
. Ryanodine: more specialized, involved in excitation-contraction coupling in muscle and Ca induced Ca release in neurons
. IP3R: more ubiquitous role, present in all types of cells
AChE inhibitors
. Used for glaucoma, inc. GI motility, and myasthenia Gravis
Disposition of NE neurotransmitter
. Presynaptic: uptake by active pump uptake-1 (inhibited by cocaine and tricyclic antidepressants), after uptakes by presynaptic neuron, NE metabolized by MAO enzyme
. Target cells: uptake-2 pump (not cocaine sensitive), after uptake in postsynaptic cell, NE metabolized by COMT
. Diffusion: detectable in plasma
